Download INTRODUCTION TO PHARMACOLOGY

SAMUEL AGUAZIM ( MD)


The study of the interaction between
chemicals and living systems
Pharmacology is the science that deals with
the study of therapeutic agents.

A drug is broadly defined as any chemical
agent that affects biologic systems
What is Pharmacology ?
Pharmacokinetics
Pharmacodynamics
What the body does to drug
What the drug does to body
Pharmacology
Pharmacotherapeutics
The study of the use of drugs
Pharmacocognosy
Identifying crude materials as drugs
Toxicology

Pharmacokinetics- describes “ what the
body does to the drug.” this includes topics
such as absorption, distribution, metabolism
and excretion of drugs.

Pharmacodynamics- describes “ what the
drug does to the body.” specifically, it deals
with the biochemical and physiological
effects of drugs and their mechanisms of
action

Pharmacotherapeutics- describes the use of
drugs for the prevention, diagnosis and
treatment of disease.

Toxicology- describes the undesirable effects
of therapeutic agents, poisons and pollutants
on biologic systems

Pharmacokinetics describes actions of the body on
drugs, including the principles of drug absorption,
distribution, biotransformation (metabolism) and
excretion

Absorption is the rate at which and extent to
which a drug moves form its site of
administration



Route of administration- the intravenous route is
most effective.
Blood flow- highly vascularized organs such as the
small intestine have the greatest absorbing ability
Surface area available- absorption of a drug is
directly proportional to the surface area available



Solubility of a drug- the ratio of hydrophilic to
lipophilic properties that a drug has will
determine whether the drug can permeate
cell membranes
Drugs-drugs interaction- when given in
combination, drugs can either enhance or
inhibit one another’s absorption.
pH- a drug’s acidity or alkalinity affects its
charge which affects absorption


Many drugs are either weak acids or weak
bases. Acidic drugs are uncharged when
protonated while
Basic drugs are charged when protonated

Generally, a drug will pass through cell
membranes more easily if it is uncharged.
Therefore, the amount of drug absorbed
depends upon its ration of charged to
uncharged species, which is determined by
the ambient pH at the site of administration
and the pKa(negative log of dissociation
constant) of the drug

The fraction of administered drug that gains
access to its site of action or a biologic fluid
that allows access to the site of action.




What is the bioavailability of an intravenously
injected drug?
100%- because all of the drug enters the
systemic circulation
what is the bioavailability of any drug that is
not intravascularly injected?
Less than 100%- because some of the drug
may not be absorbed or it may become
inactivated.


1. first pass hepatic metabolism
2. all of the factors that affect absorption
(i.e., blood flow, drug solubility, drug-drug
interactions, route of administration)
Parenteral
(IV)
Inhaled
Oral
Transdermal
Topical
Parenteral
(SC, IM)
Rectal






Alimentary
Parenteral
Inhalation
Topical
Transdermal
subcutaneous


Oral-commonest route
Advantages: convenience/patient
compliance and the utilization of the small
intestine, which is specialized for absorption
because of its large surface area.





Buccal( between gum and cheeks).
Advantages: allows direct absorption into
the venous circulation
Sublingual( under the tongue)
Nitroglycerin is often given by this route.
Advantage: allows the drug to drain into the
superior vena cava, thus bypassing hepatic
first-pass metabolism


Rectal (suppository)-useful when the oral
route is unavailable due to vomiting or loss of
consciousness:
Advantages: approximately 50% of drug
absorbed from the rectum will bypass the
liver


1. intravenous- direct injection into the
vascular system.
Advantage: most rapid and potent mode of
administration, because 100% of drugs enters
circulation




Intramuscular
Advantages: usually more rapid and
complete absorption than with oral
administration.
Minimizes hazards of intravascular injection
Location important
 Deltoid - rapid
 Thigh - moderate
 Buttocks - slowest
 Difference in blood supply & distance
 Subcutaneous-under skin
 Advantages: same as intramuscular
 Intrathecal- under sheath of nerve fibers, spinal cord,
or brain

Advantage: in cases of acute CNS infections
or spinal anesthesia, drugs can be more
effective if injected directly into the spinal
subarachnoid space.




What category of drugs is commonly
administered by inhalation?
Answer: pulmonary agents
How are inhaled drugs administered?
By machine aerosolization or vaporization
Copyright, 2004, CNS Productions,
Inc.
1




When is topical administration used?
Usually for treatment of localized disease( e.g
psoriasis, acne, eye infections)
When is transdermal administration used?
For sustained release of a drug- for example
nicotine patches.

Is define as the process by which a drugs
leaves the bloodstream and enters the
interstitium or the cells of the tissue



1. Passive diffusion: it is the most common
mode of drug transport which makes a drug
move from higher concentration to one of
low concentration
2. Transport by special carrier proteins3. Active transport. The energy for this
mechanism comes from dephosphorylation
of adenosine triphosphosphate



Blood flow
Capillary permeability- the structure of
capillaries varies depending on the organ.
E.g. in the brain the junction between cells is
very tight. In the liver and spleen, the junction
between endothelial cells is wide. Which
allows large molecules to pass through.
Binding to plasma proteins such as
albumin- this will limit access to cellular
compartments

Drug structure- small lipophilic molecules
will be able to distribute to more
compartments than will large polar molecules


Why does the body biotransform drugs?
The lipophilic properties of drugs that allow
them to pass through the cell membranes
hinder elimination. Therefore, drugs are
modified to become more polar so that
elimination can occur more quickly.
Two main modification occur in
biotransformation:
 Phase 1: oxidation, reduction(dehydrogenation)
and hydrolysis
 occur in endoplasmic reticulum
 Phase 2: formation of a covalent linkage
between functional groups on the parent drug
and another substrate(i.e glucuronate, acetic
acid, glutathione and sulfate)
 Occur in cytosol
 they both occur in the LIVER






Genetic differences
Induction of the cytochrome P-450( increase
biotransformation)
Inhibition of the cutochrome P-450 system
Disease of the liver
Age and gender



Yes. In general, drugs will be inactivated or
biotransformed according to one of two
general chemistry principle.
First order kinetics
Zero-order kinetics


Process by which a constant percentage of
substrate is metabolized per unit time.
The higher the concentration of drug, the
greater the absolute amount of drug
biotransformed or excreted per unit of time


Process by which a constant amount of drug
is metabolized per unit of time regardless of
the drug concentration.
Alcohol is metabolized according to zero
order kinetics.

Is define as the process by which a drug or
metabolite is removed from the body



Excretion is the removal of a drug from the body
Secretion occurs when the drug is actively
transported from one compartment into another.
( for example: drugs are secreted into the renal
tubule from the medullary capillaries)





Renal- urine is one of the most common
routes of elimination
Fecal
Respiration- primarily for anesthetic gases
and vapors
Breast milk
skin